This invention relates to a process for producing a 4-alkoxycarbonyl-2-oxazolidinone compound which is useful as synthetic starting materials or intermediates of pharmaceuticals and agricultural chemicals.
4-Alkoxycarbonyl-2-oxazolidinone compound can be easily led to a xcex2-hydroxy-xcex1-amino acid compound which is useful as pharmaceuticals, or pharmaceutical intermediates or starting materials in accordance with the method described in, for example, Journal of American Chemical Society, 118, pp. 3584-3590 (1996) by subjecting to alkali hydrolysis using an aqueous potassium hydroxide solution.
As the conventional method for preparing 4-alkoxycarbonyl-2-oxazolidinone compound, the following methods have been known.
{circumflex over (1)}: In Nihon Kagakukai Zasshi, vol. 82, p. 1075, (1961), there is disclosed a method in which phosgene is acted on D,L-threonine in the presence of sodium hydroxide, and esterifying with methanol and hydrochloric acid to obtain 5-methyl-4-methoxycarbonyl-2-oxazoline. This method is not industrially sufficient method in the point of using xcex2-hydroxy-xcex1-amino acid compound which is difficultly obtained as a starting material.
{circumflex over (2)}: In Nihon Kagakukai Zasshi, vol. 82, p. 1075, (1961), there is disclosed a method in which N-Cbz-D,L-arothreonine is subjected to ring opening in the presence of sodium hydroxide, and esterifying with methanol and hydrochloric acid to obtain 5-methyl-4-methoxycarbonyl-2-oxazolidinone. This method is also not industrially sufficient method in the point of using, as a starting material, xcex2-hydroxy-xcex1-amino acid compound the starting material of which is difficultly obtained.
{circumflex over (3)}: In Journal of Organic Chemistry, vol. 44, p. 3967, (1979), there is disclosed a method in which N-carbobenzyloxyglycine ethyl ester is reacted with benzaldehyde in the presence of lithium diisopropylamide to obtain 5-phenyl-4-methoxycarbonyl-2-oxazolidinone. However, this method is not industrially satisfied preparation method in the point that lithium diisopropylamide handling of which is difficult must be used.
{circumflex over (4)}: In Tetrahedron Letters, vol. 29, p. 2069 (1988), there is disclosed a method of obtaining 3-methyl-5-(1-methyl-3-pentenyl)-4-methoxycarbonyl-2-oxazolidinone by reacting 3-(1-methyl-3-pentenyl)-2,3-epoxy-1-propanol and methyl iso-cyanate to obtain 4-hydroxymethyloxazolidine and oxidizing the resulting compound with a chromium compound and esterifying with diazomethane. However, the method is not industrially sufficient method in the points that the steps are long and a chromium compound or diazomethane which is difficultly used industrially must be used.
Accordingly, in the above-mentioned conventionally known methods {circumflex over (1)}, {circumflex over (2)}, {circumflex over (3)} and {circumflex over (4)}, there are problems that the starting materials are difficultly obtained, a starting material which is difficultly used for industrial purpose must be used, the steps are long and yield is low, so that a novel preparation method of 4-alkoxycarbonyl-2-oxazolidinone compound which can overcome these problems has been desired.
An object of the present invention is to provide a preparation method of a 4-alkoxycarbony-2-oxazolidinon compound which is available as a synthetic starting material or an intermediate of medicine or agricultural chemicals.
The present inventors have investigated to solve the above-mentioned problems and as a result, they have found that by reacting 5-alkoxy-2(3H)oxazolone compound which has not yet been described in the references and an aldehyde compound in the presence of a Lewis acid catalyst, a 4-alkoxycarbonyl-2-oxazolidinone compound can be obtained easily with high yield to accomplish the present invention. That is, the present invention is as mentioned below.
That is, the present invention related to a process for producing a 4-alkoxycarbonyl-2-oxazolidinone compound represented by the formula (III): 
wherein R1 represents a hydrogen atom, a C1 to C10 alkyl group which may be substituted, a C3 to C10 cycloalkyl group which may be substituted, a C2 to C10 alkenyl group which may be substituted or a phenyl group which may be substituted, R2 represents a hydrogen atom, a C1 to C10 alkyl group which may be substituted, a phenyl group which may be substituted or a C2 to C10 alkenyl group which is not substituted, R3 represents a C1 to C10 alkyl group which may be substituted, a C3 to C10 cycloalkyl group which may be substituted,o a C2 to C10 alkenyl group which may be substituted (provided that a 2-alkenyl group is excluded), or a phenyl group which may be substituted, and R4 represents a hydrogen atom, a C1 to C20 alkyl group which may be substituted, a C2 to C20 alkenyl group which may be substituted, a C3 to C10 cycloalkyl group which may be substituted, a C2 to C20 alkynyl group which may be substituted, a C6 to C20 aryl group which may be substituted, a 5- or 6-membered heteroaromatic ring group having 1 or 2 hetero atoms selected from N, O and S which may be substituted, a C1 to C6 alkoxycarbonyl group which
may be substituted, an acetyl group or a benzoyl group, which comprises reacting a 5-alkoxy-2(3H)oxazolone compound represented by the formula (I): 
wherein R1, R2 and R3 have the same meanings as defined above,
and an aldehyde compound represented by the formula (II):
R4CHOxe2x80x83xe2x80x83(II)
wherein R4 has the same meaning as defined above, in the presence of a Lewis acid catalyst to obtain the title compound.
In the following, the present invention is explained in detail.
The process of the present invention can be shown, for example by the following reaction formula (I): 
wherein R1, R2, R3 and R4 have the same meanings as defined above.
In the present invention, R1 in the compound (I) represented by the formula (I) represents a hydrogen atom, a C1 to C10 alkyl group which may be substituted, a C3 to C10 cycloalkyl group which may be substituted or a C2 to C10 alkenyl group which may be substituted or a phenyl group which may be substituted.
xe2x80x9cThe C1 to C10 alkyl group which may be substitutedxe2x80x9d represented by R1 means (1) xe2x80x9ca C1 to C10 alkyl group having no substituentxe2x80x9d or (2) xe2x80x9ca C1 to C10 alkyl group having a substituent(s)xe2x80x9d.
As xe2x80x9cthe C1 to C10 alkyl group having no substituentxe2x80x9d of (1), there may be mentioned, for example, a straight or branched C1 to C10 alkyl group such as a methyl group, an ethyl group, a propyl group (including an isomer), a butyl group (including isomers thereof), a pentyl group (including isomers thereof), a hexyl group (including isomers thereof), a heptyl group (including isomers thereof), an octyl group (including isomers thereof), a nonyl group (including isomers thereof) or a decyl group (including isomers thereof), etc.
As the substituent for xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group, a benzyloxy group, a phthalimino group, an acylamino group, an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion, a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion, a halogen atom, an aryl group which may be substituted, xe2x80x9ca 5- or 6-membered heteroaromatic ring group (hereinafter also referred to as xe2x80x9ca heteroaromatic ring groupxe2x80x9d) containing 1 or 2 hetero atoms selected from N, O and Sxe2x80x9d, or a C1 to C10 alkoxy group which may be substituted. Incidentally, the number of the substituent(s) and the position thereof is not limited.
xe2x80x9cThe aryl group which may be substitutedxe2x80x9d as the substituent for xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d of (2) means (2-1) xe2x80x9can aryl group having no substituentxe2x80x9d or (2-2) xe2x80x9can aryl group having a substituent(s)xe2x80x9d.
As xe2x80x9cthe aryl group having no substituentxe2x80x9d of (2-1), there may be mentioned, for example, a phenyl group, a naphthyl group, an anthryl group or a phenanthryl group, etc.
As xe2x80x9cthe aryl group having a substituent(s)xe2x80x9d of (2-2), there may be mentioned, for example, a nitro group; a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; a straight or branched C1 to C6 alkyl group; or a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent are not limited.
xe2x80x9cThe heteroaromatic ring group which may be substitutedxe2x80x9d as a substituent of xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d of (2) means (2-3) xe2x80x9ca heteroaromatic ring group having no substituentxe2x80x9d or (2-4) xe2x80x9ca heteroaromatic ring group having a substituent(s)xe2x80x9d.
As (2-3) xe2x80x9cthe heteroaromatic ring group having no substituentxe2x80x9d, there may be mentioned, for example, a furyl group, a thienyl group, a pyrrolyl group, a 2H-pyrrolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, an imidazolyl group, a pyrazolyl group, a pyranyl group, a pyridyl group, a pyridazyl group, a pyrimidyl group or a pyrazinyl group, etc.
As (2-4) xe2x80x9cthe heteroaromatic ring group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a nitro group; a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; a straight or branched C1 to C6 alkyl group; or a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent are not limited.
As (2-5) xe2x80x9cthe C1 to C10 alkoxy group having no substituentxe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C10 alkoxy group such as a methoxy group, an ethoxy group, a propoxy group (including an isomer), a butoxy group (including isomers thereof), a pentyloxy group (including isomers thereof), a hexyloxy group (including isomers thereof), a heptyloxy group (including isomers thereof), an octyloxy group (including isomers thereof), a nonyloxy group (including isomers thereof) or a decyloxy group (including isomers thereof), etc.
As the substituent for (2-6) xe2x80x9cthe C1 to C10 alkoxy group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a benzyloxy group; a phenoxy group; a methoxyethoxy group; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion or a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent are not limited.
xe2x80x9cThe cycloalkyl group which may be substitutedxe2x80x9d represented by R1 in the compound (I) represented by the formula (I) means (3) xe2x80x9ca C3 to C10 cycloalkyl group having no substituentxe2x80x9d or (4) xe2x80x9ca C3 to C10 cycloalkyl group having a substituent(s)xe2x80x9d.
As (3) xe2x80x9cthe C3 to C10 cycloalkyl group having no substituentxe2x80x9d, there may be mentioned, for example, a C3 to C10 cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, a cyclodecyl group, a bornyl group or an adamantyl group, etc.
As the substituent for (4) xe2x80x9cthe C3 to C10 cycloalkyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group; a benzyloxy group; a benzosulfonyl group; an acylamino group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; a straight or branched C1 to C6 alkyl group; an aryl group which may be substituted or a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent are not limited.
xe2x80x9cThe C2 to C10 alkenyl group which may be substitutedxe2x80x9d represented by R1 in the compound (I) represented by the formula (I) has the same meanings as (5) xe2x80x9ca C2 to C10 alkenyl group having no substituentxe2x80x9d or (6) xe2x80x9ca C2 to C10 alkenyl group having a substituent(s)xe2x80x9d.
As (5) xe2x80x9cthe C2 to C10 alkenyl group having no substituentxe2x80x9d, there may be mentioned, for example, a straight or branched C2 to C10 alkenyl group such as an ethenyl group, a propenyl group (including its isomer), a butenyl group (including isomers thereof), a pentenyl group (including isomers thereof), a hexenyl group (including isomers thereof), a heptenyl group (including isomers thereof), an octenyl group (including isomers thereof), a nonenyl group (including isomers thereof) or a decenyl group (including isomers thereof), etc.
As the substituent for (6) xe2x80x9cthe C2 to C10 alkenyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; an aryl group which may be substituted; a heteroaromatic ring group which may be substituted or a straight or branched C1 to C6 alkoxy group. Incidentally, the number of the substituent and the position thereof are not particularly limited.
xe2x80x9cThe phenyl group which may be substitutedxe2x80x9d represented by R1 in the compound (I) represented by the formula (I) means a phenyl group or xe2x80x9ca phenyl group having a substituent(s)xe2x80x9d. As the substituent for xe2x80x9cthe phenyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C6 alkyl group, a nitro group, a benzyloxy group, a halogen atom, an acylamino group and a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent(s) are not limited.
Specific examples of such R1 may include, for example, a hydrogen atom, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, a 2-cyanoethyl group, a 1-methoxycarbonylethyl group, a 2-trimethylsilyloxyethyl group, a 2-benzyloxyethyl group, a 2-trifluoroethyl group, a 2-chloroethyl group, a benzyl group, a 4-nitrobenzyl group, a cyanobenzyl group, a 4-methoxycarbonylbenzyl group, a 4-trimethysilyloxybenzyl group, a 4-benzyloxybenzyl group, a 3,4-difluorobenzyl group, a 4-methylbenzyl group, an 2-methylbenzyl group, a 3,4-dichlorobenzyl group, an 2-fluorobenzyl group, a 4-fluorobenzyl group, a 2,4-dimethylbenzyl group, a 4-isopropylbenzyl group, a 4-tert-butylbenzyl group, an 2-methoxybenzyl group, a 3-methoxybenzyl group, a 4-methoxybenzyl group, a 3,4-dimethoxybenzyl group, a 2,4-dimethoxybenzyl group, a 2-ethoxybenzyl group, a 4-isopropoxybenzyl group, a 4-tert-butoxybenzyl group, a 1-phenylethyl group, a 1-(4-nitrophenyl)ethyl group, a 1-(4-bromophenyl)ethyl group, a 1-(4-fluorophenyl)ethyl group, a 1-(4-methoxyphenyl)ethyl group, a 1-(4-chlorophenyl)ethyl group, a 1-(1-naphthyl)ethyl group, a 1-(2-naphthyl)ethyl group, a diphenylmethyl group, a di(4-chlorophenyl)methyl group, a di(4-methoxyphenyl)methyl group, a trityl group, a 1-(2-phenanthryl)ethyl group, a 1-(9-anthranyl)ethyl group, a furfuryl group, a 2-thienylmethyl group, a 2-pyridylmethyl group, a 3-pyridylmethyl group, an isothiazolylmethyl group, a 2-pyrazolylethyl group, a (2H-pyrrolyl) group, an (N-methylpyrrolyl)methyl group, an isoxazolylmethyl group, a 2-methyoxyethyl group, a 2-ethoxyethyl group, a 2-(n-propoxy)ethyl group, a 2-isopropoxyethyl group, a 3-(n-butoxy)propyl group, 2-(sec-butoxy)ethyl group, a 2-(tert-butoxy)ethyl group, a 2-hexyloxyethyl group, a 2-methoxy-n-butyl group, a 2-(tert-butoxy)-1,1-dimethyl-ethyl group, a 2-octyloxyethyl group, a 2-nonyloxyethyl group, a 2-heptyloxyethyl group, a 2-methoxyethoxyethyl group, a 2-(benzyloxymethoxy)-ethyl group, a 2-(2-methoxyethoxymethoxy)ethyl group, a 2-(ethoxymethoxy)-ethyl group, a 2-(phenoxymethoxy)-ethyl group, a 2-formaminoethyl group, a 2-acetaminoethyl group, a 2-chloroacetaminoethyl group, a 2-benzoylaminoethyl group, a 2-phenylacetaminoethyl group, a 2-methoxycarbonylaminoethyl group, a 2-ethoxycarbonylaminoethyl group, a 2-allyloxycarbonylaminoethyl group, a 2-tert-butoxycarbonylaminoethyl group, a 2-benzyloxycarbonylaminoethyl group, an ethynyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group, a decenyl group, a 2-cyanoethynyl group, a 1-methoxycarbonyl-2-propenyl group, a 1-trimethylsilyloxymethyl-2-propenyl group, a 1-benzyloxymethyl-2-propenyl group, a cinnamyl group, a 2-methoxymethyl-2-propenyl group, a 2-ethoxymethyl-2-propenyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, a cyclodecyl group, a 1-methoxycarbonylcyclopropyl group, a 2-phenylcyclopropyl group, a 2-fluorocyclopropyl group, a 2-chlorocyclopropyl group, a 2-benzyloxycyclopropyl group, a 1-cyanocyclopentyl group, a 2-norbornyl group, a bornyl group, a 1-adamanthyl group, a 4-methylcyclohexyl group, a 2-methylcyclohexyl group, a 2,3-dimethylcyclohexyl group, a 2-methoxycarbonylcyclohexyl group, a 2-methoxycyclohexyl group, a 2-trimethylsilyloxycyclohexyl group, a 2-benzyloxycyclohexyl group, a 4-benzyloxycyclohexyl group, 4-tert-butylcyclohexyl group, a menthyl group, a 8-phenylmenthyl group, a phenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 4-tert-butylphenyl group, a 3,4-dimethylphenyl group, a 4-ethylphenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, a 2-bromophenyl group, a 3-bromophenyl group, a 4-bromophenyl group, a 2-iodophenyl group, a 4-iodophenyl group, a 4-methoxyphenyl group, a 3,4-dimethoxyphenyl group, a 3,4-dibenzyloxyphenyl group, a 4-benzyloxyphenyl group, a 2-benzyloxyphenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group and a 4-nitrophenyl group, etc.
In the present invention, R2 in the compound (I) represented by the formula (I) represents a hydrogen atom, a C1 to C10 alkyl group which may be substituted, a phenyl group which may be substituted or a C2 to C10 alkenyl group which is not substituted.
xe2x80x9cThe C1 to C10 alkyl group which may be substitutedxe2x80x9d represented by R2 means (7) xe2x80x9ca C1 to C10 alkyl group having no substituentxe2x80x9d or (8) xe2x80x9ca C1 to C10 alkyl group having a substituent(s)xe2x80x9d.
As xe2x80x9cthe C1 to C10 alkyl group having no substituentxe2x80x9d of (7) may be mentioned, for example, the above-mentioned straight or branched C1 to C10 alkyl group.
As the substituent of (8) xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a phthalimide group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; an aryl group which may be substituted; a heteroaromatic ring group which may be substituted; a straight or branched C1 to C10 alkoxy group; an acylamino group; a C1 to C10 alkylthio group or a benzylthio group. Incidentally, the number and the position of the substituent are not limited.
xe2x80x9cThe aryl group which may be substitutedxe2x80x9d as a substituent for (8) xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d means (8-1) xe2x80x9can aryl group having no substituentxe2x80x9d or (8-2) xe2x80x9can aryl group having a substituent(s)xe2x80x9d.
As (8-1) xe2x80x9cthe aryl group having no substituentxe2x80x9d, there may be mentioned, for example, a phenyl group or a naphthyl group.
As the substituent for (8-2) xe2x80x9cthe aryl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C6 alkyl group; a nitro group; a benzyloxy group; a cyano group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; an acylamino group or a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent are not limited.
xe2x80x9cThe heteroaromatic ring group which may be substitutedxe2x80x9d as a substituent for (8) xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d means (8-3) xe2x80x9ca heteroaromatic ring group having no substituentxe2x80x9d or (8-4) xe2x80x9ca heteroaromatic ring group having a substituent(s)xe2x80x9d.
As (8-3) xe2x80x9cthe heteroaromatic ring group having no substituentxe2x80x9d, there may be mentioned, for example, a furyl group, a thienyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an indolyl group or an imidazolyl group, etc.
The heteroaromatic ring group of (8-4) xe2x80x9cthe heteroaromatic ring group having a substituent (s)xe2x80x9d has the same meaning as (8-3) xe2x80x9cthe heteroaromatic ring group having no substituentxe2x80x9d. As the substituent for (8-4) xe2x80x9cthe heteroaromatic ring group having a substituent (s)xe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C10 alkyl group; a halogen atom or an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion. Incidentally, the number and the position of the substituent are not limited.
In the present invention, xe2x80x9cthe phenyl group which may be substitutedxe2x80x9d represented by R2 in the compound (I) represented by the formula (I) means a phenyl group or xe2x80x9ca phenyl group having a substituent(s)xe2x80x9d. As the substituent for xe2x80x9cthe phenyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a benzyloxy group, a halogen atom, a straight or branched C1 to C6 alkoxy group; an acylamino group or a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion, etc. Incidentally, the number and the position of the substituent(s) are not limited.
In the present invention, xe2x80x9cthe C2 to C10 alkenyl group which is not substitutedxe2x80x9d represented by R2 in the compound (I) represented by the formula (I) may be mentioned, for example, a straight or branched C2 to C10 alkenyl group.
Specific examples of such R2 may include, for example, a hydrogen atom, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, a 2-methoxycarbonylethyl group, a 3-methoxycarbonylpropyl group, a 4-methoxycarbonylbutyl group, a 1-trimethylsilyloxyethyl group, a benzyloxymethyl group, a 1-benzyloxyethyl group, a 1-benzyloxypropyl group, a 1-benzyloxybutyl group, a methoxymethyl group, a 1-tert-butoxyethyl group, a 1-ethoxyethyl group, a 1-hexyloxyethyl group, an isopropoxymethyl group, a n-propoxymethyl group, a 2-methylthioethyl group, a 2-ethylthioethyl group, a methylthiomethyl group, a butylthiomethyl group, a tert-butylthiomethyl group, a benzylthiomethyl group, a 2-trifluoroethyl group, a trifluoromethyl group, a 2-chloroethyl group, a fluoromethyl group, a 1-fluorobutyl group, a 1-fluoro-1-phenylmethyl group, a 1-fluoroethyl group, a 2-acetylaminoethyl group, a 3-benzoylaminopropyl group, a 4-formylaminobutyl group, a 4-acetylaminobutyl group, a 4-chloroacetaminobutyl group, a 4-phenylacetaminobutyl group, a 4-methoxycarbonylaminobutyl group, a 4-ethoxycarbonylaminobutyl group, a 4-allyloxycarbonylaminobutyl group, a 4-tert-butyloxycarbonylaminobutyl group, a 4-benzyloxycarbonyl-aminobutyl group, a 4-phthaloylaminobutyl group, a benzyl group, a 4-nitrobenzyl group,-a 4-cyanobenzyl group, a 4-methoxycarbonylbenzyl group, a 4-trimethylsilyloxybenzyl group, a 4-benzyloxybenzyl group, a 3,4-dichlorobenzyl group, a 2-fluorobenzyl group, a 4-fluorobenzyl group, a 3,4-difluorobenzyl group, a 4-methylbenzyl group, a 2-methylbenzyl group, a 2,4-dimethylbenzyl group, a 4-isopropylbenzyl group, a 4-tert-butylbenzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group, a 4-methoxybenzyl group, a 3,4-dimethoxybenzyl group, a 2,4-dimethoxybenzyl group, a 2-ethoxybenzyl group, a 4-isopropoxybenzyl group, a 4-tert-butoxybenzyl group, a 4-tert-butoxycarbonylaminobenzyl group, a 4-acetylaminobenzyl group, a 2-benzyloxycarbonylaminobenzyl group, a 1-phenylethyl group, a 1-(4-nitrophenyl) ethyl group, a 1-(4-bromophenyl)ethyl group, a 1-(4-fluorophenyl)ethyl group, a 1-(4-methoxyphenyl)ethyl group, a 1-(4-chlorophenyl)ethyl group, a 1-(1-naphthyl)ethyl group, a 1-(2-naphthyl)ethyl group, a diphenylmethyl group, a di(4-chlorophenyl)methyl group, a di(4-methoxyphenyl) methyl group, a trityl group, a 2-phenylethyl group, a 2-(4-benzyloxyphenyl)ethyl group, a furfuryl group, a thienylmethyl group, a thiazolylmethyl group, an isoxazolylmethyl group, an oxazolylmethyl group, a (4-N-methylimidazolyl)methyl group, an N-methylindolylmethyl group, a phenyl group, a 2-fluorophenyl group, a 4-benzyloxyphenyl group, a 4-methoxyphenyl group, a 2-chlorophenyl group, a 4-bromophenyl group, a 4-acetaminophenyl group, a 4-benzyloxycarbonylaminophenyl group, an ethynyl group, a 1-propenyl group, a 2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-pentenyl group, a 2-pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group or a decenyl group.
In the present invention, R3 in the compound (I) represented by the formula (I) represents a C1 to C10 alkyl group which may be substituted, a C3 to C10 cycloalkyl group which may be substituted, a C2 to C10 alkenyl group which may be substituted (provided that a 2-alkenyl group is excluded) or a phenyl group which may be substituted.
xe2x80x9cThe C1 to C10 alkyl group which may be substitutedxe2x80x9d represented by R3 in the compound (I) represented by the formula (I) means (9) xe2x80x9ca C1 to C10 alkyl group having no substituentxe2x80x9d or (10) xe2x80x9ca C1 to C10 alkyl group having a substituent(s)xe2x80x9d.
As (9) xe2x80x9cthe C1 to C10 alkyl group having no substituentxe2x80x9d, there may be mentioned, for example, the above-mentioned straight or branched C1 to C10 alkyl group.
As the substituent for (10) xe2x80x9cthe C1 to C10 alkyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; an acylamino group; a halogen atom; xe2x80x9cthe aryl group which may be substitutedxe2x80x9d as xe2x80x9cmentioned in (8-1) and (8-2)xe2x80x9d or a C1 to C10 alkoxy group as xe2x80x9cmentioned in (2-5)xe2x80x9d.
xe2x80x9cThe C3 to C10 cycloalkyl group which may be substitutedxe2x80x9d represented by R3 in the formula (I) represented by the formula (I) means (11) xe2x80x9ca C3 to C10 cycloalkyl group having no substituentxe2x80x9d or (12) xe2x80x9ca C3 to C10 cycloalkyl group having a substituent(s)xe2x80x9d.
(11) xe2x80x9cThe C3 to C10 cycloalkyl group having no substituentxe2x80x9d has the same meaning as xe2x80x9cthe C3 to C10 cycloalkyl group having no substituentxe2x80x9d mentioned in (3), and (12) xe2x80x9cthe C3 to C10 cycloalkyl group having a substituent(s)xe2x80x9d have the same meaning as xe2x80x9cthe C3 to C10 cycloalkyl group having a substituent(s) mentioned in (4).
xe2x80x9cThe C2 to C10 alkenyl group which may be substituted (provided that a 2-alkenyl group is excluded)xe2x80x9d represented by R3 in the formula (I) represented by the formula (I) means (13) xe2x80x9ca C2 to C10 alkenyl group having no substituent (provided that a 2-alkenyl group is excluded) or (14) xe2x80x9ca C2 to C10 alkenyl group having a substituent(s) (provided that a 2-alkenyl group is excluded)xe2x80x9d.
As (13) xe2x80x9cthe C2 to C10 alkenyl group having no substituent (provided that a 2-alkenyl group is excluded)xe2x80x9d, there may be mentioned, for example, a straight or branched C2 to C10 alkenyl group having no substituent (provided that a 2-alkenyl group is excluded)xe2x80x9d.
Incidentally, when the process represented by the reaction formula (I) of the present invention as mentioned below is carried out by using a compound represented by the formula (II) containing a 2-alkenyl group in the molecule as R3, the compound represented by the formula (I) cannot be obtained.
As (14) xe2x80x9cthe C2 to C10 alkenyl group having a substituent(s) (provided that a 2-alkenyl group is excluded)xe2x80x9d, there may be mentioned, for example, a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; an acylamino group; a halogen atom; an aryl group which may be substituted xe2x80x9cas mentioned in (8-1) and (8-2)xe2x80x9d or a C1 to C10 alkoxy group xe2x80x9cas mentioned in (2-5)xe2x80x9d. Incidentally, the number and the position of the substituent(s) are not limited.
xe2x80x9cThe phenyl group which may be substitutedxe2x80x9d represented by R3 in the compound (I) represented by the formula (I) means a phenyl group or xe2x80x9ca phenyl group having a substituent(s)xe2x80x9d. As the substituent for xe2x80x9cthe phenyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C6 alkyl group, a nitro group, and the above-mentioned halogen atom.
Specific examples of such R3 may include, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, a 2-methoxycarbonylethyl group, a 3-methoxycarbonylpropyl group, a 4-methoxycarbonylbutyl group, a 1-benzyloxyethyl group, a 3-benzyloxypropyl group, a 3-benzyloxyisobutyl group, a 2-methoxyethyl group, a 2-tert-butoxyethyl group, a 2-ethoxyethyl group, a 2-hexyloxyethyl group, a 2-isopropoxyethyl group, a 3-n-propoxypropyl group, a 2-trifluoroethyl group, a trifluoromethyl group, a 2-chloroethyl group, a fluoromethyl group, a 2-fluoroethyl group, a 1-fluorobutyl group, a 1-fluoro-1-phenylmethyl group, a 1-fluoroethyl group, a 2-bromoethyl group, a 2-acetylaminoethyl group, a 3-benzoylaminopropyl group, a 4-formylaminobutyl group, a 4-acetylaminobutyl group, a 4-chloroacetaminobutyl group, a 4-phenylacetaminobutyl group, a 4-methoxycarbonylaminobutyl group, a 4-ethoxycarbonylaminobutyl group, a 4-allyloxycarbonylaminobutyl group, a 4-tert-butyloxycarbonylaminobutyl group, a 4-benzyloxycarbonylaminobutyl group, a benzyl group, a 4-nitrobenzyl group, a 4-trimethylsilyloxybenzyl group, a 4-benzyloxybenzyl group, 3,4-dichlorobenzyl group, a 2-fluorobenzyl group, a 4-fluorobenzyl group, a 3, 4-difluorobenzyl group, a 4-methylbenzyl group, a 2-methylbenzyl group, a 2,4-dimethylbenzyl group, a 4-isopropylbenzyl group, a 4-tert-butylbenzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group, a 4-methoxybenzyl group, a 3,4-dimethoxybenzyl group, a 2,4-dimethoxybenzyl group, a 2-ethoxybenzyl group, a 4-isopropoxybenzyl group, a 4-tert-butoxybenzyl group, a 4-tert-butoxycarbonylaminobenzyl group, a 4-acetylaminobenzyl group, a 2-benzyloxycarbonylbenzyl group, a 1-phenylethyl group, a 1-(4-nitrophenyl)ethyl group, a 1-(4-bromophenyl)ethyl group, a 1(4-fluorophenyl)ethyl group, a 1-(4-methoxyphenyl)ethyl group, a 1-(4-chlorophenyl)ethyl group, a 1-(1-naphthyl)ethyl group, a 1(2-naphthyl)ethyl group, a diphenylmethyl group, a di(4-chlorophenyl)methyl group, a di(4-methoxyphenyl)methyl group, a trityl group, a 2-phenylethyl group, a 2-(4-benzyloxyphenyl)ethyl group, an ethenyl group, a 1-propenyl group, a 1-butenyl group, a 3-butenyl group, a 1-pentenyl group, a 3-pentenyl group, a 4-pentenyl group, a 5-hexenyl group, a 6-heptenyl group, a 7-octenyl group, a 8-nonyl group, a 9-decenyl group, a 3-methoxycarbonyl-1-propenyl group, a 1-methoxycarbonylethynyl group, a 2-benzyloxymethylethynyl group, a 3-chloro-4-pentenyl group, a 4-chloro-3-butenyl group, a 4-phenyl-3-butenyl group, a 5-phenyl-4-pentenyl group, a 5-benzyloxy-3-butenyl group, a 6-methoxy-3-hexenyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, a cyclodecyl group, a 1-methoxycarbonylcyclopropyl group, a 2-phenylcyclopropyl group, a 2-fluorocyclopropyl group, a 2-chlorocyclopropyl group, a 1-benzyloxymethylcyclopentyl group, a 3-cyanocyclopentyl group, a 2-acetaminocyclohexyl group, a 2-benzoylaminocyclohexyl group, a 2-methoxycarbonylaminocyclohexyl group, a 2-tert-butoxycarbonylaminocyclohexyl group, a 2-benzyloxycarbonylaminocyclohexyl group, a 2-methoxycyclohexyl group, a 2-chlorocyclohexyl group, a 2-norbornyl group, a bornyl group, a 2-adamantyl group, an N-benzosulfonyl-N-(3,5-dimethylphenyl)-aminobornyl group, a 4-methylcyclohexyl group, a 2-methyl-cyclohexyl group, a 2,3-dimethylcyclohexyl group, a 1-methoxycarbonylcyclohexyl group, a 2-trimethylsiloxycyclohexyl group, a 2-benzyloxycyclohexyl group, a 4-benzyloxycyclohexyl group, a 4-tert-butylcyclohexyl group, a menthyl group, a 8-phenylmenthyl group, a phenyl group, a 2-methylphenyl group, a 4-methylphenyl group, a 2,5-di-tert-butyl-4-methyl group, a 4-tert-butyl group, a 2-chlorophenyl group, a 4-chlorophenyl group, a 4-fluorophenyl group, a 2-fluorophenyl group, a 3-chlorophenyl group or a 4-nitrophenyl group, etc.
As the specific compounds of the compound (I) represented by the formula (I), there may be mentioned, for example, 3-benzyl-5-methoxy-2(3H)oxazolone, 3-benzyl-4-methyl-5-methoxy-2(3H)oxazolone, 3-(4-nitrobenzyl)-5-ethoxy-2(3H)oxazolone, 3-benzyl-5-(l)-menthyloxy-2(3H)oxazolone, 3-(4-methylbenzyl)-4-methyl-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-5-methoxy-2(3H)oxazolone, 3-((S)-1-phenylethyl)-5-isopropoxy-2(3H)oxazolone, 3-((R)-1-phenylethyl)-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-5-methoxy-2(3H)oxazolone, 3-di-phenylmethyl-4-methyl-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-5-(l)-menthyloxy-2(3H)oxazolone, 3-diphenylmethyl-5-((1S,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl-oxy)-2(3H)oxazolone, 3-benzyl-5-((1S,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxy)-2(3H)oxazolone, 3-diphenylmethyl-4-isopropyl-5-isopropoxy-2(3H)oxazolone, 3-diphenylmethyl-4-phenylmethyl-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-4-isobutyl-5-ethoxy-2(3H)oxazolone, 3-diphenylmethyl-4-(sec-butyl)-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-4-(benzyloxyphenyl)-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-4-methoxycarbonylmethyl-5-isopropoxy-2(3H)oxazolone, 3-diphenylmethyl-4-benzyloxymethyl-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-4-(2-methoxycarbonylethyl)-5-methoxy-2(3H)oxazolone, 3-diphenylmethyl-4-(4-BocNH-butyl)-5-methoxy-2(3H)oxazolone (Boc=tert-butoxy-carbonyl), 3-(1-(1-naphthyl)ethyl)-4-isopropyl-5-isopropoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-phenylmethyl-5-methoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-isobutyl-5-ethoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-(sec-butyl)-5-methoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-(benzyloxyphenyl)-5-methoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonylmethyl-5-isopropoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-benzyloxymethyl-5-methoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-(2-methoxycarbonylethyl)-5-methoxy-2(3H)oxazolone, 3-(1-(1-naphthyl)ethyl)-4-(4-BocNH-butyl)-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-isopropyl-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-phenylmethyl-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-isobutyl-5-ethoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-(sec-butyl)-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-(benzyloxyphenyl)-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-methoxycarbonylmethyl-5-ethoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-benzyloxymethyl-5-methoxy-2(3H)-oxazolone, 3-(1-phenylethyl)-4-(2-methoxycarbonylethyl)-5-methoxy-2(3H)oxazolone, 3-(1-phenylethyl)-4-(4-BocNH-butyl)-5-methoxy-2(3H)oxazolone, 3-((R)-1-(1-naphthyl)ethyl)-5-methoxy-2(3H)oxazolone, 3-furfuryl-4-ethyl-5-methoxy-2(3H)-oxazolone, 3-furfuryl-4-ethyl-5-(4-pentenyl)oxy-2(3H)oxazolone, 3-isopropyl-5-methoxy-2(3H)oxazolone, 3-benzyl-5-methoxy-2(3H)oxazolone, 3-isopropyl-4-methyl-5-methoxy-2(3H)oxazolone, 3-isopropyl-4-methyl-5-ethoxy-2(3H)oxazolone, 3-isopropyl-4-methyl-5-cyclohexyloxy-2(3H)oxazolone, 3-methyl-5-isopropoxy-2(3H)oxazolone, 3-((R)-1-(1-naphthyl)-ethyl)-5-isopropoxy-2(3H)oxazolone, 3-((R)-1-phenylethyl)-4-methyl-5-methoxy-2(3H)oxazolone, 3-((S)-1-phenylethyl)-5-phenoxy-2(3H)oxazolone, 3-diphenylmethyl-4-methyl-5-phenoxy-2(3H)oxazolone, 3-phenyl-4-methyl-5-methoxy-2(3H)oxazolone, 3-(p-chlorophenyl)-4-ethyl-5-methoxy-2(3H)oxazolone, 3-(o-chlorophenyl)-4-methyl-5-methoxy-2(3H)oxazolone, 3-(3,4-dimethoxyphenyl)-4-methyl-5-methoxy-2(3H)oxazolone and 3-phenyl-5-methoxy-2(3H)oxazolone, etc.
The 5-alkoxy-2(3H)oxazolone (Compound (I)) represented by the formula (I) of the present invention can be produced according to the method of the reaction formula (2) as mentioned below. (Reaction formula 2) 
wherein R1, R2 and R3 have the same meanings as defined above.
The first step is to produce a compound represented by the formula (VIII) (hereinafter also referred to as Compound (VIII), and can be accomplished by reacting an N-substituted-xcex1-amino acid ester compound represented by the formula (VII) (hereinafter also referred to as Compound (VII)) with a chlorocarbonylating agent such as phosgene, trichloromethyl chloroformate, etc. in the presence of an inorganic base such as sodium carbonate, etc., or an organic base such as triethylamine, etc., or the like in a solvent.
The second step is to produce a compound represented by the formula (I), and the compound (I) can be obtained by subjecting the compound represented by the formula (VIII) to intramolecular cyclization reaction in the presence of an organic base such as triethylamine or tri-n-propylamine, etc., or an inorganic base such as sodium carbonate, etc.
In the present invention, R4 in the compound (II) represented by the formula (II) represents a hydrogen atom, a C1 to C20 alkyl group which may be substituted, a C2 to C20 alkenyl group which may be substituted, a C3 to C10 cycloalkyl group which may be substituted, a C2 to C20 alkynyl group which may be substituted, a C6 to C20 aryl group which may be substituted, a 5- or 6-membered heteroaromatic ring group containing 1 or 2 hetero atoms selected from N, O and S, which may be substituted, a C1 to C6 alkoxycarbonyl group which may be substituted, an acetyl group or a benzoyl group.
xe2x80x9cThe C1 to C20 alkyl group which may be substitutedxe2x80x9d represented by R4 means (15) xe2x80x9ca C1 to C20 alkyl group having no substituentxe2x80x9d or (16) xe2x80x9ca C1 to C20 alkyl group having a substituent(s)xe2x80x9d.
As (15) xe2x80x9cthe C1 to C20 alkyl group having no substituentxe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C20 alkyl group such as a methyl group, an ethyl group, a propyl group (including an isomer), a butyl group (including isomers thereof), a pentyl group (including isomers thereof), a hexyl group (including isomers thereof), a heptyl group (including isomers thereof), an octyl group (including isomers thereof), a nonyl group (including isomers thereof), a decyl group (including isomers thereof), an undecyl group (including isomers thereof), a dodecyl group (including isomers thereof), a tridecyl group (including isomers thereof), a tetradecyl group (including isomers thereof), a pentadecyl group (including isomers thereof), a hexadecyl group (including isomers thereof), a heptadecyl group (including isomers thereof), an octadecyl group (including isomers thereof), a nonadecyl group (including isomers thereof) or an eicosyl group (including isomers thereof), etc.
As the substituent for (16) xe2x80x9cthe C1 to C20 alkyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group; a benzyloxy group; a phthalimino group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion; an acylamino group; a halogen atom; an aryl group as xe2x80x9cdescribed in (2-1) and (2-2)xe2x80x9d; a heteroaromatic ring group as xe2x80x9cdescribed in (8-3) and (8-4)xe2x80x9d or a C1 to C10 alkoxy group as xe2x80x9cdescribed in (2-5) and (2-6)xe2x80x9d.
xe2x80x9cThe C2 to C20 alkenyl group which may be substitutedxe2x80x9d represented by R4 in the compound (II) represented by the formula (II) has the same meaning as (17) xe2x80x9ca C2 to C20 alkenyl group having no substituentxe2x80x9d or (18) xe2x80x9ca C2 to C20 alkenyl group having a substituent(s)xe2x80x9d.
As (17) xe2x80x9cthe C2 to C20 alkenyl group having no substituentxe2x80x9d, there may be mentioned, for example, a straight or branched C2 to C20 alkenyl group.
As the substituent for (18) xe2x80x9cthe C2 to C20 alkenyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group; a benzyloxy group; an acylamino group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion; a halogen atom; an aryl group as xe2x80x9cdescribed in (2-3) and (2-4)xe2x80x9d; a C3 to C10 cycloalkyl group or a heteroaromatic ring group.
xe2x80x9cThe C3 to C10 cycloalkyl group which may be substitutedxe2x80x9d represented by R4 in the compound (II) represented by the formula (II) has the same meaning as (19) xe2x80x9ca C3 to C10 cycloalkyl group having no substituentxe2x80x9d or (20) xe2x80x9ca C3 to C10 cycloalkyl group having a substituent(s)xe2x80x9d.
As (19) xe2x80x9cthe C3 to C10 cycloalkyl group having no substituentxe2x80x9d, there may be mentioned, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group or a cyclodecyl group.
As the substituent for (20) xe2x80x9cthe C3 to C10 cycloalkyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion; an acylamino group; a halogen atom; an aryl group or a C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent(s) are not limited.
xe2x80x9cThe C2 to C20 alkynyl group which may be substitutedxe2x80x9d represented by R4 in the compound (II) represented by the formula (II) has the same meaning as (21) xe2x80x9ca C2 to C20 alkynyl group having no substituentxe2x80x9d or (22) xe2x80x9ca C2 to C20 alkynyl group having a substituent(s)xe2x80x9d.
As (21) xe2x80x9cthe C2 to C20 alkynyl group having no substituentxe2x80x9d, there may be mentioned, for example, a straight or branched C2 to C20 alkynyl group.
As the substituent for (22) xe2x80x9cthe C2 to C20 alkynyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a cyano group; a benzyloxy group; an acylamino group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion; a halogen atom or an aryl group.
xe2x80x9cThe C6 to C20 aryl group which may be substitutedxe2x80x9d represented by R4 in the compound (II) represented by the formula (II) has the same meaning as (23) xe2x80x9ca C6 to C20 aryl group having no substituentxe2x80x9d or (24) xe2x80x9ca C6 to C20 aryl group having a substituent(s)xe2x80x9d.
As (23) xe2x80x9cthe C6 to C20 aryl group having no substituentxe2x80x9d, there may be mentioned, for example, a phenyl group, a naphthyl group, an anthranyl group, a phenanthryl group, etc.
The aryl group of (24) xe2x80x9cthe C6 to C20 aryl group having a substituent(s)xe2x80x9d has the same meaning as (23) xe2x80x9cthe C6 to C20 aryl group having no substituentxe2x80x9d.
As the substituent for (24) xe2x80x9cthe C6 to C20 aryl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a nitro group; a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion; a halogen atom; a straight or branched C1 to C6 alkyl group or a straight or branched C1 to C6 alkoxy group.
xe2x80x9cThe 5- or 6-membered heteroaromatic ring group containing 1 or 2 hetero atoms selected from N, O and S, which may be substitutedxe2x80x9d represented by R4 in the compound (II) represented by the formula (II) has the same meaning as (25) xe2x80x9ca 5- or 6-membered heteroaromatic ring group containing 1 or 2 hetero atoms selected from N, O and S having no substituentxe2x80x9d or (26) xe2x80x9ca 5- or 6-membered heteroaromatic ring group containing 1 or 2 hetero atoms selected from N, O and S having a substituent(s)xe2x80x9d.
As the heteroaromatic ring group of (25) xe2x80x9cthe 5- or 6-membered heteroaromatic ring group containing 1 or 2 hetero atoms selected from N, O and S having no substituentxe2x80x9d, there may be mentioned, for example, a furyl group, a thienyl group, a pyrrolyl group, a 2H-pyrrolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, an imidazolyl group, a pyrazolyl group, a pyranyl group, a pyridyl group, a pyridazyl group, a pyrimidyl group or a pyrazinyl group, etc.
As the substituent for (26) xe2x80x9cthe 5- or 6-membered heteroaromatic ring group containing 1 or 2 hetero atoms selected from N, O and S having a substituent(s)xe2x80x9d, there may be mentioned, for example, a nitro group; a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different, straight or branched C1 to C6 alkyl group portion; a halogen atom; a straight or branched C1 to C6 alkyl group; or a straight or branched C1 to C6 alkoxy group. Incidentally, the number and the position of the substituent are not limited.
xe2x80x9cThe C1 to C6 alkoxycarbonyl group which may be substitutedxe2x80x9d represented by R4 in the compound (II) represented by the formula (II) means (27) xe2x80x9ca C1 to C6 alkoxycarbonyl group having no substituentxe2x80x9d or (28) xe2x80x9ca C1 to C6 alkoxycarbonyl group having a substituent(s)xe2x80x9d.
As the alkoxycarbonyl group of (27) xe2x80x9cthe C1 to C6 alkoxycarbonyl group having no substituentxe2x80x9d, there may be mentioned, for example, a straight or branched C1 to C6 alkoxycarbonyl group such as a methoxycarbonyl group, an ethoxycarbonyl group, a n-propionyloxycarbonyl group, an isopropyloxycarbonyl group, a n-butoxycarbonyl group, a tert-butoxycarbonyl group, a n-pentyloxycarbonyl group, a n-hexyloxycarbonyl group, etc.
As the substituent for (28) xe2x80x9cthe C1 to C6 alkoxycarbonyl group having a substituent(s)xe2x80x9d, there may be mentioned, for example, a nitro group; a cyano group; a benzyloxy group; an alkoxycarbonyl group having a straight or branched C1 to C6 alkyl group portion; a trialkylsilyloxy group having the same or different straight or branched C1 to C6 alkyl group portion; a halogen atom; a straight or branched C1 to C6 alkoxy group, etc. Incidentally, the number and the position of the substituent(s) are not limited.
Specific examples of such R4 may include, for example, a hydrogen atom, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, a n-hexyl group, a n-heptyl group, a n-octyl group, a n-nonyl group, a n-decyl group, a n-undecyl group, a n-dodecyl group, a n-tridecyl group, a n-tetradecyl group, a n-pentadecyl group, a n-hexadecyl group, a n-heptadecyl group, a n-octadecyl group, a n-nonadecyl group, an n-eicosyl group, a methoxymethyl group, an acetyloxymethyl group, a benzyloxymethyl group, a tert-butyloxymethyl group, a 1-methoxyethyl group, a 1-benzyloxyethyl group, a 1-benzyloxypropyl group, a 1-benzyloxybutyl group, a 1-phenylethyl group, a 2-phenylethyl group, a 3-phenylpropyl group, a phenylmethyl group, a 2-chloroethyl group, a 2-fluoroethyl group, a monofluoromethyl group, a trifluoromethyl group, a BocNH-methyl group (Boc=tert-butoxycarbonyl), a CbzNH-methyl group (Cbz=benzyloxycarbonyl), a benzoyl group, an acetyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a menthyloxycarbonyl group, a methylthiomethyl group, a methoxycarbonylmethyl group, a 3-BocNH-propyl group, a 4-BocNH-butyl group, an acylaminoethyl group, a 2-benzyloxypropyl group, a cyclohexylmethyl group, a 1-methyl-3-methoxycarbonylbutyl group, a 1-cyclohexylethyl group, a 2-(N-Boc-piperidy)methyl group, a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-butenyl group, a 2-butenyl group, a styryl group, a 4-nitrostyryl group, a 4-chlorostyryl group, a 4-methylstyryl group, a 4-methoxystyryl group, a 3-phenyl-2-propenyl group, a 3-phenyl-1-propenyl group, a 2-hexenyl group, a 2-heptenyl group, a 2-pentenyl group, a 2,4-hexadienyl group, a 1-methyl-3-pentenyl group, a 1-tetradecynyl group, a 1-pentadecynyl group, a 1-hexadecenyl group, a 2,3,12-tribenzyloxy-3-heptadecynyl group, a 2,3,12-tri-tert-butyldimethylsilyloxy-3-heptadecynyl group, a 2-furylvinyl group, a 2-cyclohexyl-vinyl group, a phenylethyl group, a 3-phenyl-1-propargyl group, a propargyl group, a 1-butynyl group, a 1-pentynyl group, a 1-hexynyl group, a 2-heptynyl group, a 1-octynyl group, a 1-nonenyl group, a cyclopropyl group, a cyclohexyl group, a cyclobutyl group, a cyclopentyl group, a 2-phenylcyclopropyl group, a 2,2-dimethoxycarbonylcyclopropyl group, a phenyl group, a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-methoxyphenyl group, a 3-methoxyphenyl group, a 4-benzyloxyphenyl group, a 3-benzyloxyphenyl group, a 2-benzyloxyphenyl group, a 3,4-dibenzyloxyphenyl group, a 3,4-methylenedioxyphenyl group, a 3,4-dimethoxyphenyl group, a 4-nitrophenyl group, a 3,5-dibromo-4-benzyloxyphenyl group, a 3,5-dichloro-4-benzyloxyphenyl group, a p-tert-butyldimethylsilyloxyphenyl group, a furyl group, a thienyl group, a thiazolyl group, an isoxazolyl group, an oxazolyl group, a 4-N-methylimidazolyl group, a N-methylindolyl group, etc.
As the compound represented by the formula (II), there may be mentioned aldehydes having the substituent mentioned as R4, more specifically, preferred are benzaldehyde, 4-methoxybenzaldehyde, 2-methoxybenzaldehyde, 3,4-methylenedioxybenzaldehyde, 3,4-dimethoxybenzaldehyde, 4-nitrobenzaldehyde, 2-nitrobenzaldehyde, naphthylaldehyde, acetaldehyde, propionaldehyde, n-butylaldehyde, isobutyl aldehyde, cinnamaldehyde, hydrocinnamaldehyde, crotonaldehyde, phenylacetaldehyde, xcex1-benzyloxypropionaldehyde, methylglycidiate, acrolein, tetradecenal and benzyloxyacetaldehyde; more preferred are benzaldehyde, 3,4-methylenedioxybenzaldehyde, 3,4-dimethoxybenzaldehyde, isobutyl aldehyde, cinnamaldehyde, hydrocinnamaldehyde and methylglycidiate.
As the compound (III), compounds comprising a combination of the substituents described as R1, R2, R3 and R4 as mentioned above may be mentioned. As the specific compound (III) thereof, the following compounds may be mentioned.
There may be mentioned, for example, 3-diphenylmethyl-4-methoxycarbonyl-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(3,4-dimethoxyphenyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(4-benzyloxyphenyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(3,4-methylenedioxyphenyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(3,4-dibenzyloxyphenyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(3,4-ditrimethylsilyloxyphenyl)-2-oxazolidinone, 3-diphenylmethyl-4-ethoxycarbonyl-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-isopropoxycarbonyl-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-tert-butoxycarbonyl-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-((l)-menthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-(8-phenylmenthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-isopropyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(2-phenylethyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-methyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(3-BocNH-propyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(methoxycarbonylmethyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-tridecyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(1-methyl-3-pentenyl)-2-oxazolidione, 3-methyl-4-methoxycarbonyl-5-(1-methyl-3-pentenyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-(1-pentadecenyl)-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-hydroxymethyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-benzyloxymethyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-acetyloxymethyl-2-oxazolidinone, 3-diphenylmethyl-4-methoxycarbonyl-5-trimethylsilyloxymethyl-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-phenyl-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-(4-benzyloxyphenyl)-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-(3,4-methylenedioxyphenyl)-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-(3,4-dimethoxyphenyl)-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-isopropyl-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-(2-phenylethyl)-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-methyl-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-benzyloxymethyl-2-oxazolidinone, 3-(1-phenylethyl)-4-methoxycarbonyl-5-methoxycarbonylmethyl-2-oxazolidinone, 3-(1-phenylethyl)-4-((l)-menthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-(1-phenylethyl)-4-((l)-menthyloxycarbonyl)-5-isopropyl-2-oxazolidinone, 3-(1-phenylethyl)-4-((l)-menthyloxycarbonyl)-5-(2-phenylethyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-((l)-menthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(3,4-dimethoxyphenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-isopropoxycarbonyl-5-(3,4-methylenedioxyphenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-isopropoxycarbonyl -5-isopropyl-2-oxazolidinone, 3-((1-(-1-naphthyl)ethyl)-4-isopropoxycarbonyl-5-(2-phenylethyl)-2-oxazolidinone, 3-(1-(-naphthyl)ethyl)-4-isopropoxycarbonyl-5-(2-phenylethynyl)-2-oxazolidinone, 3-(1-(-naphthyl)ethyl)-4-isopropoxycarbonyl-5-methyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-isopropoxycarbonyl-5-cyclopropyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-cyclohexyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-isopropoxycarbonyl-5-(1-propenyl)-2-oxazolidinone, 3-(1-(1-naphtyl)ethyl-4-methoxycarbonyl-5-(4-benzyloxyphenyl)-2-oxazolidin-one, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(3,4-methylenedioxyphenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(3,4-dibenzyloxyphenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(3,4-ditrimethylsilyloxyphenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-ethoxycarbonyl-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-isopropoxycarbonyl-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-tert-butoxycarbonyl-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-((l)-menthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-(8-phenylmenthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-isopropyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(2-phenylethyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-methyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(3-BocNH-propyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(methoxycarbonylmethyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-tridecyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(1-methyl-3-pentenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-(1-pentadecenyl)-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-hydroxymethyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-benzyloxymetyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-acetyloxymethyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4-methoxycarbonyl-5-trimethylsilyloxymethyl-2-oxazolidinone, 3-(1-(1-naphthyl)ethyl)-4,5-dimethoxycarbonyl-2-oxazolidinone, 3-diphenylmethyl-4,5-dimethoxycarbonyl-2-oxazolidinone, 3-(1-phenylethyl)-4,5-dimethoxycarbonyl-2-oxazolidinone, 3-diphenylmethyl-4-(8-phenylmenthyloxycarbonyl)-5-isopropyl-2-oxazolidinone, 3-diphenylmethyl-4-(8-phenylmenthyloxycarbonyl)-5-(2-phenylethyl)-2-oxazolidinone, 3-benzyl-4-(8-phenylmenthyloxycarbonyl)-5-phenyl-2-oxazolidinone, 3-benzyl-4-(8-phenylmenthyloxy-carbonyl)-5-isopropyl-2-oxazolidinone, 3-benzyl-4-(8-phenyl-menthyloxycarbonyl)-5-(2-phenylethyl)-2-oxazolidinone, 3-phenyl-4-methoxycarbonyl-4-methyl-5-phenyl-2-oxazolidinone, 3-(o-chlorophenyl)-4-methoxycarbonyl-5-isopropyl-2-oxazolidinone, 3-phenyl-4-methoxycarbonyl-4-methyl-5-methyl-2-oxazolidinone, 3-(p-chlorophenyl)-4-methoxycarbonyl-4-ethyl-5-phenyl-2-oxazolidinone, 3-phenyl-4-isopropyloxycarbonyl-4-methyl-5-phenyl-2-oxazolidinone, 3-diphenylmethyl-4-phenoxycarbonyl-4-methyl-5-phenyl-2-oxazolidinone, 3-(1-phenylethyl)-4-phenoxycarbonyl-5-phenyl-2-oxazolidinone, 3-phenyl-4-methoxycarbonyl-5-isopropyl-2-oxazolidinone, etc.
As the Lewis acid catalyst to be used in the present invention, the following organometallic compounds, halides, or trifluoromethane sulfonates of elements from Group 2 (Group IIa) to Group 4 (Group IVa) (provided that carbon is excluded) of the Periodic Table, halides or trifluoromethane sulfonates of a Lanthanoid group metal can be specifically used.
Specifically, there may be mentioned the compound represented by the following formula (IV):
R5nXmMxe2x80x83xe2x80x83(IV)
wherein R5 represents a C1 to C10 alkyl group or a C6 to C20 aryl group; X represents a halogen atom; M represents Al, B, Sn or Ti; m and n each represents a number of 0, 1, 2, 3 or 4; provided that m+n is 2, 3 or 4.
The alkyl group represented by R5 in the compound (IV) represented by the formula (IV) represents a C1 to C10 alkyl group, and there may be mentioned, for example, a straight or branched C1 to C10 alkyl group such as a methyl group, an ethyl group, a propyl group (including an isomer), a butyl group (including isomers thereof), a pentyl group (including isomers thereof), a hexyl group (including isomers thereof), a heptyl group (including isomers thereof), an octyl group (including isomers thereof), a nonyl group (including isomers thereof) or a decyl group (including isomers thereof), etc., preferably a C1 to C6 alkyl group, more preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group.
The aryl group represented by R5 in the compound (IV) represented by the formula (IV) has the same meaning as the aryl group as xe2x80x9cdescribed in (23) and (24)xe2x80x9d.
X in the compound (IV) represented by the formula (IV) represents, for example, a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc. M represents Al, B, Sn or Ti. m and n each represents a number of 0, 1, 2, 3 or 4. However, m+n is 2, 3 or 4.
As the specific compounds of the compound (IV) represented by the formula (IV), there may be mentioned, for example, trialkyl aluminum such as trimethyl aluminum, triethyl aluminum, tripropyl aluminum, triisopropyl aluminum, tri-n-butyl aluminum, triisobutyl aluminum, tri-sec-butyl aluminum, tri-tert-butyl aluminum, tripentyl aluminum, trihexyl aluminum, trioctyl aluminum, tridecyl aluminum, etc.; dialkyl aluminum halide such as dimethyl aluminum chloride, diethyl aluminum chloride, diethyl aluminum bromide, diisobutyl aluminum chloride, etc.; dialkyl aluminum hydride such as diethyl aluminum hydride, diisobutyl aluminum hydride, etc., an alkyl aluminum dihalide such as methyl aluminum dichloride, ethyl aluminum dichloride, isobutyl aluminum dichloride, ethyl aluminum dibromide, etc.; aluminum halides such as aluminum (III) chloride, aluminum (III) bromide, aluminum (III) iodide, aluminum (III) fluoride, etc.; boron trihalides such as boron trifluoride, boron trichloride, boron tribromide, etc.; trihaloboranes such as trifluoroborane, trichloroborane, tribromoborane, etc.; triarylboranes such as triphenylborane, tri(4-fluorophenyl)borane, tris(penta-fluorophenyl)borane, etc.; arylborane dihalides such as phenyl dichloroborane, 4-chlorophenyl dichloroborane, phenyl dibromoborane, etc.; arylborane halides such as dimethylfluoroborane, diphenylfluoroborane, etc.; trialkyl boranes such as triethyl borane, tributyl borane, etc.; tin halides such as tin (IV) chloride, tin (II) chloride, tin (IV) bromide, tin (II) bromide, etc.; tetraalkyl tins such as tetraethyl tin, tetrabutyl tin, tetraisopropyl tin, etc.; tetraaryl tins such as tetraphenyl tin, etc.; alkylaryl tins such as benzyltriphenyl tin, pentafluorophenyltrimethyl tin, etc.; trialkyl tin halides such as trimethyl tin bromide, trimethyl tin chloride, triethyl tin bromide, tributyl tin chloride, tribenzyl tin chloride, etc.; triaryl tin halides such as triphenyl tin chloride, etc.; trialkyl tin hydrides such as tributyl tin hydride, etc.; titanium halides such as titanium (IV) chloride, titanium (IV) bromide, titanium (IV) iodide, titanium (IV) fluoride, etc.
Also, as a Lewis acid, the compound represented by the formula (V):
(R6O)nxe2x80x2Xmxe2x80x2Mxe2x80x83xe2x80x83(V)
wherein R6 represents a C1 to C10 alkyl group or a C6 to C20 aryl group; X represents a halogen atom; M represents Al, B, Sn or Ti; mxe2x80x2 and nxe2x80x2 each represents a number of 0, 1, 2, 3 or 4; provided that mxe2x80x2+nxe2x80x2 is 3 or 4, can be also mentioned.
The C1 to C10 alkyl group or the C6 to C20 aryl group represented by R6 in the compound (V) represented by the formula (V) have the same meanings as the C1 to C10 alkyl group or the C6 to C20 aryl group represented by R5, respectively.
X in the compound (V) represented by the formula (V) represents, for example, a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc. M represents Al, B, Sn or Ti. mxe2x80x2 and nxe2x80x2 each represents a number of 0, 1, 2, 3 or 4. However, mxe2x80x2+nxe2x80x2 is 3 or 4.
As the specific compounds of the compound (IV) represented by the formula (IV), there may be mentioned, for example, alkoxytitanium trihalides such as trichloromethoxy titanium, trichloroethoxy titanium, trichloroisopropoxy titanium, trichloro-n-butoxy titanium, tribromoethoxy titanium, tri-bromoisobutoxy titanium, etc.; dialkoxy titanium dihalides such as dichlorodimethoxy titanium, dichlorodiethoxy titanium, dichlorodi-n-butoxy titanium, dichlorodiisopropoxy titanium, dibromodiethoxy titanium, etc.; trialkoxy titanium halides such as chlorotrimethoxy titanium, chlorotriethoxy titanium, chlorotri-n-butoxy titanium, bromotriethoxy titanium, etc.; titanium (IV) alkoxides such as titanium (IV) methoxide, titanium (IV) ethoxide, titanium (IV) isopropoxide, titanium (IV) isobutoxide, titanium (IV) n-butoxide, etc.; dialkyl aluminum alkoxides such as dimethyl aluminum methoxide, diethyl aluminum ethoxide, diethyl aluminum isopropoxide, dibutyl aluminum butoxide, etc.; dialkyl aluminum aryloxides such as diethyl aluminum phenoxide, diethyl aluminum (4-fluorophenoxide), etc.; aluminum (III) alkoxides such as aluminum (III) methoxide, aluminum (III) isoprodpoxide, aluminum (III) butoxide, etc.; aluminum (III) aryloxides such as aluminum (III) phenoxide, etc.; triaryloxy boranes such as triphenoxy borane, etc.; trialkoxy boranes such as trimethoxy borane, tributoxy borane, etc.; diaryloxyborane dihalides such as chlorodiphenoxy borane, bromodiphenoxy borane, fluorodiphenoxy borane, etc.; diaryloxy borane dihalides such as dichlorophenoxy borane, etc.
Moreover, as the Lewis acid, a compound represented by the formula (VI):
R7R8R9SiXxe2x80x2xe2x80x83xe2x80x83(VI)
Wherein R7, R8 and R9 each independently represents a C1 to C10 alkyl group or a C6 to C20 aryl group; Xxe2x80x2 represents a halogen atom or xe2x80x94OSO2CF3.
The C1 to C10 alkyl group or the C6 to C20 aryl group represented by R7, R8 and R9 in the compound (VI) represented by the formula (VI) have the same meanings as the C1 to C10 alkyl group or the C6 to C20 aryl group represented by R5, respectively.
Xxe2x80x2 represents, for example a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc., or a xe2x80x94OSO2CF3 group.
Specific compound represented of the compound (VI) represented by the formula (VI) may include, for example, trialkylsilyl halides such as trimethylsilyl chloride, trimethylsilyl bromide, trimethylsilyl iodide, triethylsilyl chloride, triethylsilyl bromide, triethylsilyl iodide, tert-butyldimethylsilyl chloride, tert-butyldimethylsilyl bromide, tert-butyldimethylsilyl iodide, triisopropylsilyl chloride, triisopropylsilyl bromide, triisopropylsilyl iodide, etc.; trialkylsilyl triflates such as trimethylsilyl triflate, triethylsilyl triflate, tert-butyldimethylsilyl triflate, triisopropylsilyl triflate, etc.; triarylsilyl halides such as triphenylsilyl chloride, triphenylsilyl bromide, triphenylsilyl iodide, etc.; triarylsilyl triflates such as triphenylsilyl triflate, etc.; alkylarylsilyl halides such as tert-butyl-diphenylsilyl chloride, tert-butyldiphenylsilyl bromide, tert-butyldiphenylsilyl iodide, methyldiphenylsilyl chloride, methyldiphenylsilyl bromide, methyldiphenylsilyl iodide, etc.; alkylarylsilyl triflates such as tert-butyldiphenylsilyl triflate, methyldiphenylsilyl triflate, etc.
In addition, there may be mentioned metal halides or triflates such as zirconium (IV) chloride, zinc (II) chloride, zinc (II) bromide, iron (III) chloride, iron (II) chloride, iron (III) bromide, iron (II) bromide, iron (III) iodide, iron (II) iodide, magnesium chloride, magnesiumbromide, tin triflate (II), etc.; halides or triflates of rare earth metals such as lanthanum (III) triflate, lanthanum (III) chloride, praseodymium (III) triflate, neodymium (III) triflate, samarium (III) triflate, samarium (II) iodide, samarium (III) chloride, europium (III) triflate, gadolinium (III) triflate, dysprosium (III) triflate, holmium (III) triflate, erbium (III) triflate, ytterbium (III) triflate, lutetium (III) triflate, scandium (III) triflate, cerium (III) chloride, etc.
The 4-alkoxycarbonyl-2-oxazolidinone compound represented by the compound (III) can be produced according to the method of the reaction formula (1) as mentioned above.
That is, the production of the compound (III) can be accomplished by reacting the 5-alkoxy-2(3H)oxazolone compound represented by the formula (I) with the aldehyde compound represented by the formula (II) in the presence of a Lewis acid catalyst in a solvent.
An amount of the Lewis acid catalyst to be used may be mentioned in a ratio of usually 0.001 to 5.0 equivalents, preferably 0.005 to 0.5 equivalent based on 1 mol of the compound (I).
As the solvent to be used, it is not particularly limited so long as it directly participate the present reaction, and there may be mentioned, for example, aromatic hydrocarbons such as benzene, toluene, xylene, etc., chlorinated hydrocarbons such as chlorobenzene, dichlorobenzene, methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc., esters such as methyl acetate, ethyl acetate, butyl acetate, etc., ethers such as diethyl ether, diisopropyl ether, dibutyl ether, dimethoxyethane, tetrahydrofuran, dioxane, etc., dimethylformamide, dimethylsulfoxide, acetonitrile, propionitrile, water, etc., but preferably toluene, xylene, methylenechloride, 1,2-dichloroethane, acetonitrile, propionitrile are preferably used.
An amount of the solvent can be used in an amount of 100 to 5000 ml, preferably 300 to 3000 ml based on 1 mol of the compound (I).
Synthetic step of the compound (III) is preferably in an inert gas atmosphere such as nitrogen, argon, helium, etc., the reaction temperature is xe2x88x92100 to 100xc2x0 C., preferably xe2x88x9280 to 40xc2x0 C., and the reaction time can be suitably selected depending on the reaction time, concentrations of the starting materials to be charged, kinds of the starting materials to be charged, etc., but generally 1 to 10 hours. An amount of the starting material is that the compound (II) is used in an amount of 0.8 to 3-fold moles, preferably 0.9 to 1.2-fold moles based on the compound (I).
As a method of obtaining a reaction mixture containing the formed compound (III) in the present invention, usual washing operation and separating operation are carried out in combination. For example, a formed salt is removed by filtration operation, the filtrate is subjected to removal operation such as washing with water, dehydration by a drier and concentration of an organic solvent whereby a crude product of the compound (III) can be obtained. When the compound is to be further purified, purification can be carried out by the conventionally known means such as column chromatography, recrystallization, etc.
Also, the compound (III) of the present invention can be obtained by applying the specific preparation method described in Examples.
Incidentally, in the resulting compound (III), xcex2-hydroxy-xcex1-amino acid can be easily derived by subjecting to hydrolysis at the ester portion or carbamate portion, as reported in, for example, J. Am. Chem. Soc., 1996, 118, 3584-3590 and it would be clear. Moreover, when R1 is a diphenylmethyl group, a benzyl group, a 1-phenylethyl group, a 1-(1-naphthyl)ethyl group, deprotection is possible by hydrogenation reaction using a Pd catalyst to give a free amino group which is also described in the above-mentioned reference and would be clear.